title: Interaction of onconase with the human ribonuclease inhibitor protein.
abstract: One of the tightest known protein-protein interactions in biology is that between members of the ribonuclease A superfamily and the ribonuclease inhibitor protein (RI). Some members of this superfamily are able to kill cancer cells, and the ability to evade RI is a major determinant of whether a ribonuclease will be cytotoxic. The archetypal cytotoxic ribonuclease, onconase (ONC), is in late-stage clinical trials for the treatment of malignant mesothelioma. We present here the first measurement of the inhibition of the ribonucleolytic activity of ONC by RI. This inhibition occurs with K(i)=0.15muM in a solution of low salt concentration.
authors.affiliation: Medical Scientist Training Program and Biophysics Graduate Program, University of Wisconsin-Madison, Madison, WI, 53706, USA.
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Turcotte
authors.affiliation: Departments of Biochemistry and Chemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA. Electronic address: rtraines@wisc.edu.
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Raines
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D006801:Humans; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D012260:Ribonucleases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics
chemical_list: D002352:Carrier Proteins; C501467:RNH1 protein, human; D012260:Ribonucleases; C058703:ranpirnase